Institute of Virology

Resistance against infection by T. gondii in mice is largely dependent on two families of IFNγ-inducible proteins, the Immunity-Related GTPases (IRG proteins) and Guanylate-binding Proteins (GBP proteins). Accumulation at the parasitophorous vacuole membrane (PVM) – a unique structure that shields the parasite from the host cell cytosol – is a prerequisite for parasite and subsequent necrotic cell death.

In human cells, depletion of tryptophan by indoleamine 2,3-dioxygenase (IDO) is known to be an IFNγ-dependent mechanism against T. gondii infections. It came apparent only recently that additional parasite control is mediated by hGBP proteins but the underlying molecular mechanism has not been revealed yet.

Inflammasomes are components of the innate immune system. They are multiprotein receptors that in response to microbial infections or tissue damage induce inflammation. Certain GBP proteins are described to be involved in inflammasome activation in context of different bacterial infections. Interestingly, T. gondii is an activator of the NLRP1 and NLRP3 inflammasomes in vivo. An association of polymorphisms in the human Nlrp1 gene with susceptibility to congenital toxoplasmosis was reported.

We aim to decipher the molecular basis of inflammasome activation upon T. gondii infection in human cells.